344 Studying the Single-cellular Substrates of Autism in a Mouse Model

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 277-278
Author(s):  
Gabriel N Friedman ◽  
Mohsen Jamali ◽  
Firas Bounni ◽  
Ziv Williams
Keyword(s):  
Acute Stress ◽  
Neuronal Response ◽  
Relevant Information ◽  
Autism Spectrum ◽  
Cellular Level ◽  
Neuronal Coding ◽  
Basic Model ◽  
Neuronal Mechanisms ◽  
Socially Relevant ◽  
Different Response

Abstract INTRODUCTION Social dysfunction is among the most prominent features of autism spectrum disorder (ASD) as well as many other developmental and neuropsychiatric conditions. What precise neuronal mechanisms are disrupted in ASD, however, are unknown. The goal of this study is to provide a basic cellular-level understanding and treatment model for ASD. METHODS We developed an alternating appetitive/aversive paradigm in which socially-paired mice experienced both acute stress and food reward while we simultaneously recorded neuronal activity from medial prefrontal cortex. We compared WT to SHANK3 -/+ mice as a model of ASD, to explore the neuronal correlates socially relevant information and its dysfunction. RESULTS >Individual medial prefrontal neurons in SHANK3 -/+ mice displayed markedly different response profiles compared to that of WT. Specifically, neurons in SHANK3 -/+ mice demonstrated little differential response when presented with another unfamiliar mouse or nonsocial totem undergoing the same condition. However, in trials where the recorded mouse and a familiar mouse both receive a negative (painful) stimulus, SHANK3 -/+ mice demonstrated a significantly attenuated firing rate in response to the conspecific mouse, while the WT mice did not show any such differences. This attenuation was not observed when the other mice received positive (rewarding) stimuli. CONCLUSION Our study reveals some of the basic neuronal coding mechanisms that are disrupted in ASD. In particular, they demonstrate that, at the cellular level, autistic mice lack the neuronal-equivalent of an “empathic” response compared to wild-type. This neuronal response may provide a foundational mechanism for egocentric behavioral often found in ASD and suggests a basic model for testing neurobiologically plausible treatments for individuals with autism.

scholarly journals Unmasking Anxiety in Autism: Explicit and Implicit Threat Dissociate Amygdala-centered Functional Connectivity

2020 ◽  
Author(s):  
Yu-Chun Chen ◽  
Chenyi Chen ◽  
Chia-Chien Liu ◽  
Róger Marcelo Martínez ◽  
Yang-Tang Fan ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Relevant Information ◽  
Autism Spectrum ◽  
Autism Spectrum Quotient ◽  
Neural Pathways ◽  
Backward Masking ◽  
Threat Processing ◽  
Fmri Study ◽  
Socially Relevant ◽  
Amygdala Reactivity

Abstract Background Anxiety is the most prevalent comorbidity in individuals diagnosed with autism spectrum disorder (ASD). Amygdala reactivity to explicit and implicit threat processing offers a platform to assess anxiety. The neural mechanisms underlying the link between anxiety and ASD remains elusive.Methods In this fMRI study, we recruited young adults with ASD (N = 31) and matched them with controls, then proceeded to assess their autistic and anxiety traits by the use of the Autism-Spectrum Quotient (AQ) and the State-Trait Anxiety Inventory (STAI-S), respectively; and scanned their amygdala reactivity in response to explicit and implicit (backward masking) perception of threatening faces.Results As compared to controls, the amygdala reactivity in ASD subjects was significantly reduced to explicit threat, but comparable to implicit threat. The correlations of the amygdala reactivity with the AQ and STAI-S were dissociated depending on threat processing (explicit or implicit). Furthermore, the amygdala in ASD relative to controls had a more negative functional connectivity with the superior parietal cortex, fusiform gyrus, and hippocampus for explicit threat, whereas a more positive connectivity with the medial prefrontal cortex, temporal pole, and hippocampus for implicit threat.Conclusion In ASD, the transmission of socially relevant information along dorsal and ventral neural pathways centered on the amygdala is dissociated depending on explicit and implicit threat processing. This dissociation, ascribed to their failure to compromise pre-existing hyperarousal, might contribute to anxiety in ASD.

scholarly journals Unmasking Anxiety in Autism: Explicit and Implicit Threatening Faces Dissociate Amygdala-centered Functional Connectivity

2020 ◽  
Author(s):  
Yu-Chun Chen ◽  
Chenyi Chen ◽  
Chia-Chien Liu ◽  
Róger Marcelo Martínez ◽  
Yang-Teng Fan ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Relevant Information ◽  
Autism Spectrum ◽  
Autism Spectrum Quotient ◽  
Neural Pathways ◽  
Threat Processing ◽  
Fmri Study ◽  
Socially Relevant ◽  
Adults With Asd ◽  
Amygdala Reactivity

Abstract Background: Anxiety is the most prevalent comorbidity in individuals diagnosed with autism spectrum disorder (ASD). Amygdala reactivity to explicit and implicit threat processing is predictive of anxiety-related symptomatology. The neural mechanisms underlying the link between anxiety and ASD remains elusive. Methods: In this fMRI study, we recruited young adults with ASD (N = 31) and matched them with controls, then proceeded to assess their autistic and anxiety traits by the use of the Autism-Spectrum Quotient (AQ) and the State-Trait Anxiety Inventory (STAI-S), respectively; and scanned their hemodynamic responses, including amygdala, in response to explicit and implicit (backwardly masked) perception of threatening faces. Results: As compared to controls, the amygdala reactivity in ASD subjects was significantly lower to explicit threat, but comparable for implicit threat. The correlations of the amygdala reactivity with the AQ and STAI-S were dissociated depending on threat processing (explicit or implicit). Furthermore, the amygdala in ASD relative to controls had a more negative functional connectivity with the superior parietal cortex, fusiform gyrus, and hippocampus for explicit threat, whereas a more positive connectivity with the medial prefrontal cortex, temporal pole, and hippocampus for implicit threat. Conclusion: In ASD, the transmission of socially relevant information along dorsal and ventral neural pathways centered on the amygdala is dissociated depending on explicit and implicit threat processing. This dissociation, ascribed to their failure to compromise pre-existing hyperarousal, might contribute to anxiety in ASD.

scholarly journals Unmasking Anxiety in Autism: Explicit and Implicit Threatening Face Stimuli Dissociate Amygdala-centered Functional Connectivity

2020 ◽  
Author(s):  
Yu-Chun Chen ◽  
Chenyi Chen ◽  
Róger Marcelo Martínez ◽  
Yang-Tang Fan ◽  
Chia-Chien Liu ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Relevant Information ◽  
Autism Spectrum ◽  
Autism Spectrum Quotient ◽  
Neural Pathways ◽  
Threat Processing ◽  
Fmri Study ◽  
Face Stimuli ◽  
Socially Relevant ◽  
Amygdala Reactivity

ABSTRACTBackgroundAnxiety is the most prevalent comorbidity in individuals diagnosed with autism spectrum disorder (ASD). Amygdala reactivity to explicit and implicit threat processing is predictive of anxiety-related symptomatology. The neural mechanisms underlying the link between anxiety and ASD remains elusive.MethodsIn this fMRI study, we recruited young adults with ASD (N = 31) and matched them with controls, then proceeded to assess their autistic and anxiety traits by the use of the Autism-Spectrum Quotient (AQ) and the State-Trait Anxiety Inventory (STAI-S), respectively; and scanned their hemodynamic responses, including amygdala, in response to explicit and implicit (backwardly masked) perception of threatening faces.ResultsAs compared to controls, the amygdala reactivity in ASD subjects was significantly lower to explicit threat, but comparable for implicit threat. The correlations of the amygdala reactivity with the AQ and STAI-S were dissociated depending on threat processing (explicit or implicit). Furthermore, the amygdala in ASD relative to controls had a more negative functional connectivity with the superior parietal cortex, fusiform gyrus, and hippocampus for explicit threat, whereas a more positive connectivity with the medial prefrontal cortex, temporal pole, and hippocampus for implicit threat.ConclusionIn ASD, the transmission of socially relevant information along dorsal and ventral neural pathways centered on the amygdala is dissociated depending on explicit and implicit threat processing. This dissociation, ascribed to their failure to compromise pre-existing hyperarousal, might contribute to anxiety in ASD.

scholarly journals Altered Salience Network Connectivity in 6-Week-Old Infants at Risk for Autism

2021 ◽  
Author(s):  
Tawny Tsang ◽  
Shulamite Green ◽  
Janelle Liu ◽  
Katherine Lawrence ◽  
Shafali Jeste ◽  
...  
Keyword(s):  
Sensory Processing ◽  
Developmental Trajectories ◽  
Brain Connectivity ◽  
External Environment ◽  
Network Connectivity ◽  
Relevant Information ◽  
Autism Spectrum ◽  
Social Attention ◽  
Salience Network ◽  
Socially Relevant

Converging evidence implicates disrupted brain connectivity in autism spectrum disorder (ASD); however, the mechanisms linking altered connectivity early in development to the emergence of ASD symptomatology remain poorly understood. Here we examined whether atypicalities in the Salience Network (SN) -- an early-emerging neural network involved in orienting attention to the most salient aspects of one's internal and external environment -- may predict the development of ASD markers such as reduced social attention and atypical sensory processing. Six-week-old infants at high-risk for ASD exhibited stronger SN connectivity with sensorimotor regions; low-risk infants demonstrated stronger SN connectivity with prefrontal regions involved in social attention. Infants with higher connectivity with sensorimotor regions had lower connectivity with prefrontal regions, suggesting a direct tradeoff between attention to basic sensory versus socially-relevant information. Early alterations in SN connectivity predicted subsequent ASD symptomatology, providing a plausible mechanistic account for the unfolding of atypical developmental trajectories associated with ASD risk.

scholarly journals Spontaneous Visual Preference for Face-Like Stimuli Is Impaired in Newly-Hatched Domestic Chicks Exposed to Valproic Acid During Embryogenesis

2021 ◽  
Vol 15 ◽  
Author(s):  
Alice Adiletta ◽  
Samantha Pedrana ◽  
Orsola Rosa-Salva ◽  
Paola Sgadò
Keyword(s):  
Relevant Information ◽  
Mental States ◽  
Domestic Chick ◽  
Autism Spectrum ◽  
Social Deficits ◽  
Social Stimuli ◽  
Domestic Chicks ◽  
Spectrum Disorders ◽  
Preference Responses ◽  
Socially Relevant

Faces convey a great amount of socially relevant information related to emotional and mental states, identity and intention. Processing of face information is a key mechanism for social and cognitive development, such that newborn babies are already tuned to recognize and orient to faces and simple schematic face-like patterns since the first hours of life. Similar to neonates, also non-human primates and domestic chicks have been shown to express orienting responses to faces and schematic face-like patterns. More importantly, existing studies have hypothesized that early disturbances of these mechanisms represent one of the earliest biomarker of social deficits in autism spectrum disorders (ASD). We used VPA exposure to induce neurodevelopmental changes associated with ASD in domestic chicks and tested whether VPA could impact the expression of the animals’ approach responses to schematic face-like stimuli. We found that VPA impairs the chicks’ preference responses to these social stimuli. Based on the results shown here and on previous studies, we propose the domestic chick as animal model to investigate the biological mechanisms underlying face processing deficits in ASD.

Handbook of Electrogastrography

2003 ◽  
Keyword(s):  
Electrical Activity ◽  
Neuromuscular Disorders ◽  
Relevant Information ◽  
Cellular Level ◽  
Clinical Practices ◽  
Physiological Basis ◽  
Gastric Dysrhythmias ◽  
History Of ◽  
Major Section ◽  
Cells Of Cajal

The Handbook of Electrogastrography is the first textbook dedicated to reviewing the physiology of gastric myelectrical activity and the measurement of this electrical activity with electrodes placed on the abdominal surface - the electrogastrogram. The Handbook is divided into three major sections. The first section (Chapters 1-3) focuses on the history of electrogastrography, electrical activity of the interstitial cells of Cajal, the cells from which gastric electrical rhythmicity emanates. The cellular level of gastric electrical rhythmicity provides an understanding of the physiological basis of the electrogastrogram signal. The second major section of the book (Chapters 4-6) incorporates the practical aspects of recording a high quality electrogastrogram and approaches to the analysis of the electrogastrogram using visual inspection and computer techniques. This section focuses on the authors' combined experience of examining EGG recordings for more than sixty years. From this rich research and clinical experience, the clinical application of EGG recordings in an approach to patients with unexplained nausea and vomiting is described. Neuromuscular disorders of the stomach involving gastric dysrhythmias are reviewed. The third major section of the book (Chapters 7-9) comprises many examples of gastric dysrythmias ranging from bradygastrias to tachygastrias and mixed dysrythmias. Current understanding of the mechanisms of gastric dysrhythmias is reviewed. Artifacts in the EGG signal, which may be confused with gastric dysrhythmias, are also presented. The Handbook of Electrogastrography will be a valuable reference for physicians interested in recording gastric electrical activity in clinical practices or in clinical research. Gastroenterologists, internists, psychologists and others with an interest in gastric myoelectrical events will also find extensive and relevant information for recording and interpreting EGGs in the Handbook.

scholarly journals Perspective influences eye movements during real-life conversation: Mentalising about self vs. others in autism

2019 ◽  
Author(s):  
Mahsa Barzy ◽  
Heather Jane Ferguson ◽  
David Williams
Keyword(s):  
Eye Movements ◽  
Real Life ◽  
Social Background ◽  
Relevant Information ◽  
Mental States ◽  
Social Attention ◽  
Typically Developing ◽  
Cognitive Mechanisms ◽  
Verbal Responses ◽  
Socially Relevant

Socio-communication is profoundly impaired among autistic individuals. Difficulties representing others’ mental states have been linked to modulations of gaze and speech, which have also been shown to be impaired in autism. Despite these observed impairments in ‘real-world’ communicative settings, research has mostly focused on lab-based experiments, where the language is highly structured. In a pre-registered experiment, we recorded eye movements and verbal responses while adults (N=50) engaged in a real-life conversation. Conversation topic either related to the self, a familiar other, or an unfamiliar other (e.g. "Tell me who is your/your mother’s/Marina’s favourite celebrity and why?”). Results replicated previous work, showing reduced attention to socially-relevant information among autistic participants (i.e. less time looking at the experimenter’s face, and more time looking around the background), compared to typically-developing controls. Importantly, perspective modulated social attention in both groups; talking about an unfamiliar other reduced attention to potentially distracting or resource demanding social information, and increased looks to non-social background. Social attention did not differ between self and familiar other contexts- reflecting greater shared knowledge for familiar/similar others. Autistic participants spent more time looking at the background when talking about an unfamiliar other vs. themselvesFuture research should investigate the cognitive mechanisms underlying this effect.

scholarly journals Neurologic Assessment of the Neurocritical Care Patient

2021 ◽  
Vol 12 ◽  
Author(s):  
Shane Musick ◽  
Anthony Alberico
Keyword(s):  
Gold Standard ◽  
Acute Stress ◽  
Cerebral Metabolism ◽  
Relevant Information ◽  
Hemodynamic Instability ◽  
Rapid Onset ◽  
Cerebral Microdialysis ◽  
Propofol Infusion Syndrome ◽  
Brain Injured ◽  
Injured Patients

Sedation is a ubiquitous practice in ICUs and NCCUs. It has the benefit of reducing cerebral energy demands, but also precludes an accurate neurologic assessment. Because of this, sedation is intermittently stopped for the purposes of a neurologic assessment, which is termed a neurologic wake-up test (NWT). NWTs are considered to be the gold-standard in continued assessment of brain-injured patients under sedation. NWTs also produce an acute stress response that is accompanied by elevations in blood pressure, respiratory rate, heart rate, and ICP. Utilization of cerebral microdialysis and brain tissue oxygen monitoring in small cohorts of brain-injured patients suggests that this is not mirrored by alterations in cerebral metabolism, and seldom affects oxygenation. The hard contraindications for the NWT are preexisting intracranial hypertension, barbiturate treatment, status epilepticus, and hyperthermia. However, hemodynamic instability, sedative use for primary ICP control, and sedative use for severe agitation or respiratory distress are considered significant safety concerns. Despite ubiquitous recommendation, it is not clear if additional clinically relevant information is gleaned through its use, especially with the contemporaneous utilization of multimodality monitoring. Various monitoring modalities provide unique and pertinent information about neurologic function, however, their role in improving patient outcomes and guiding treatment plans has not been fully elucidated. There is a paucity of information pertaining to the optimal frequency of NWTs, and if it differs based on type of injury. Only one concrete recommendation was found in the literature, exemplifying the uncertainty surrounding its utility. The most common sedative used and recommended is propofol because of its rapid onset, short duration, and reduction of cerebral energy requirements. Dexmedetomidine may be employed to facilitate serial NWTs, and should always be used in the non-intubated patient or if propofol infusion syndrome (PRIS) develops. Midazolam is not recommended due to tissue accumulation and residual sedation confounding a reliable NWT. Thus, NWTs are well-tolerated in selected patients and remain recommended as the gold-standard for continued neuromonitoring. Predicated upon one expert panel, they should be performed at least one time per day. Propofol or dexmedetomidine are the main sedative choices, both enabling a rapid awakening and consistent NWT.

scholarly journals Neural networks supporting social evaluation of bodies based on body shape

2018 ◽  
Author(s):  
Inez Greven ◽  
Paul Downing ◽  
Richard Ramsey
Keyword(s):  
Neural Networks ◽  
Body Shape ◽  
Neural Mechanism ◽  
Relevant Information ◽  
The Body ◽  
Social Judgments ◽  
Social Evaluation ◽  
Fmri Experiment ◽  
Socially Relevant ◽  
Social Inferences

Body shape cues inferences regarding personality and health, but the neural processes underpinning such inferences remain poorly understood. Across two fMRI experiments, we test the extent to which neural networks associated with body perception and theory-of-mind (ToM) support social inferences based on body shape. Participants observed obese, muscular, and slim bodies that cued distinct social inferences as pilot experiments revealed. To investigate judgment intentionality, the first fMRI experiment required participants to detect repeat presentations of bodies, whereas in fMRI Experiment 2 participants intentionally formed an impression. Body and ToM networks were localized using independent functional localisers. Experiment 1 revealed no differential network engagement for muscular or obese compared to slim bodies. By contrast, in Experiment 2, compared to slim bodies, forming impressions of muscular bodies engaged the body-network more, whereas the ToM-network was engaged more when forming impressions of obese bodies. These results demonstrate that social judgments based on body shape do not rely on a single neural mechanism, but rather on multiple mechanisms that are separately sensitive to body fat and muscularity. Moreover, dissociable responses are only apparent when intentionally forming an impression. Thus, these experiments show how segregated networks operate to extract socially-relevant information cued by body shape.

Genetic Data, Genome Understanding, and Socially Relevant Information

2021 ◽  
pp. 7-18
Author(s):  
Dara Hallinan
Keyword(s):  
Genetic Analysis ◽  
Genetic Relationships ◽  
Genomic Data ◽  
Genetic Data ◽  
Relevant Information ◽  
Significant Information ◽  
Multiple Factors ◽  
Phenotype Data ◽  
Wide Range ◽  
Socially Relevant

This chapter discusses the range of types of data which might be subject to genetic analysis to produce socially relevant information. These genetic data include raw genomic data as well as other types of data, such as phenotype data and inheritance data. Genetic analysis of these types of data is currently capable of producing a wide range of socially relevant information, including information concerning identity, genetic relationships, phenotype, health, and social and behavioural traits. It is not the case, however, that each type of genetic data can be subject to only one type of genetic analysis to produce only one type of socially relevant information. Rather, each type of genetic data, particularly genomic data, can be subject to multiple types of genetic analysis. Nor is it necessarily the case that genetic analyses produce socially relevant information which is completely accurate. Rather, the degree of accuracy of information will usually depend on multiple factors. The chapter then looks at the range of parties about whom socially significant information may be produced.

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